Previous studies have indicated that there are interactions amongst peptidergic systems in the hypothalamus to control the release of various anterior pituitary hormones. For example, it has already been shown that growth hormone releasing factor (GRF) acts within the hypothalamus to reduce the release of growth hormone (GH)- by the anterior pituitary. Our studies have shown that this action is at least in part brought about by a stimulation of somatostatin (SRIF) release. The action of GRF to stimulate SRIF release appears to be mediated via beta-endorphinergic terminals which impinge on the SRIF terminals and stimulate the release of the peptide. In this application we wish to determine the intracellular mechanisms involved in the release of SRIF in response to GRF. We hypothesize that SRIF may stimulate release of GRF and that this may be involved in its ability to act within the hypothalamus to stimulate GH release in vivo. Therefore, another aim of the grant will be to determine whether indeed SRIF stimulates GRF release both in vivo and in vitro. Other studies will concern the role of other transmitters in stimulating the release of GRF and SRIF in vivo and in vitro. These studies should enhance our knowledge of the hypothalamic control of GH release and also of the general mechanisms by which the release of brain peptides is controlled. They may have clinical relevance in the treatment of endocrine or metabolic diseases associated with altered GH secretion such as acromegaly, hypothalamic-pituitary GH deficiency, hypothyroidism, obesity and diabetes.